P669: FIXED-DURATION (FD) IBRUTINIB + VENETOCLAX FOR FIRST-LINE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL): 3-YEAR FOLLOW-UP FROM THE PHASE 2 CAPTIVATE STUDY FD COHORT
Authors: C. Moreno, W. G. Wierda, P. M. Barr, T. Siddiqi, J. N. Allan, T. J. Kipps, L. Trentin, R. Jacobs, S. Jackson, A. Tedeschi, S. Opat, R. Bannerji, B. J. Kuss, L. J. Croner, E. Szafer-Glusman, C. Zhou, A. Szoke, J. P. Dean, P. Ghia, C. S. Tam
Journal: HemaSphere (2022)

Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of first-line ibrutinib + venetoclax in CLL. The primary analysis evaluating FD treatment with ibrutinib + venetoclax was previously presented (Ghia et al., ASCO 2021). Aims: To present 3-year follow-up results from the FD cohort of CAPTIVATE. Methods: Patients aged ≤70 years with previously untreated CLL/SLL received 3 cycles of ibrutinib then 12 cycles of ibrutinib + venetoclax (ibrutinib 420 mg/day orally; venetoclax ramp-up to 400 mg/day orally). Responses were investigator assessed per iwCLL 2008 criteria. Undetectable minimal residual disease (uMRD; <10-4) was measured by 8-color flow cytometry. Serious AEs (SAEs) deemed related to ibrutinib reported >30 days after last dose of study drug were collected. Results: 159 patients were enrolled (median age 60 years), including patients with high-risk features of del(17p)/TP53 mutation (17%), unmutated IGHV (uIGHV; 56%), and complex karyotype (19%). 147 (92%) and 149 (94%) patients completed treatment with ibrutinib and venetoclax, respectively. With 1 year of additional follow-up since primary analysis, median time on study was 39 months (range 1-41). ORR was 96% and was consistent (96%-97%) in patients with high-risk features (Table). The primary endpoint of complete response (CR) including CR with incomplete bone marrow recovery (CRi) rate in patients without del(17p) (n=136) increased nominally from 56% (95% CI, 48-64) to 58% (95% CI 50-66); in all patients, CR rate increased from 55% (95% CI 48-63) to 57% (95% CI 50-65). In patients achieving CR, 93% had durable responses lasting ≥12 months post-treatment. Of patients with uMRD in peripheral blood at 3 months post-treatment, 66/85 (78%) evaluable patients maintained uMRD through 12 months post-treatment. At 36 months, PFS was 88% (95% CI 82‒92) and OS was 98% (95% CI 94-99); similar rates were seen in patients with high-risk features (Table). All patients are off treatment; no new SAEs of any kind have occurred since the primary analysis. Available data on relevant mutations in BTK, PLCɣ2, or BCL-2 at time of PD will be presented. As of January 2022, 12 patients were retreated with single-agent ibrutinib after progressive disease (treatment duration range 3-29 months); of evaluated patients, 7/9 had partial responses and 2/9 had stable disease. Image:Summary/Conclusion: Fixed duration ibrutinib + venetoclax continues to provide deep, durable responses and clinically meaningful PFS, including in patients with high-risk disease features, representing an all-oral, once-daily, chemotherapy-free FD regimen for previously untreated patients with CLL/SLL. With an additional 1 year of follow-up, no OS events or SAEs occurred. Manageable safety profile is unchanged as previously reported. To date, successful single-agent ibrutinib retreatment responses are observed.